Is Special K the Anti-Depressant We’ve Waited For?

Photo Illustration by The Daily Beast

On Tuesday, infamous pharma bro Martin Shkreli’s company Turing Pharmaceuticals inked a $95 million deal for its research program on ketamine, a powerful anesthetic turned 90s club drug nicknamed “Special K.” The research, now owned by Marina Biotech, centers on a nasal spray form of ketamine to treat severe depression.

The news came within hours of the National Institute of Health releasing a groundbreaking study on the drug’s antidepressant agents in which researchers discovered that the way the drug is metabolized has an anti-depressant effect.

The two developments, although different in nature, are indicative of the growing legitimacy a drug once known for its party-appeal has earned. Quick acting, long lasting, and capable of reducing suicidal thoughts, the drug solves many of the problems other medicines in this field create.

Is ketamine the anti-depressant we’ve all been waiting for?

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When Turing Pharmaceuticals, founded by the now disgraced Shkreli, bought the rights to the ketamine program from another biotech firm in 2015, the latter considered it a “non-core asset.” The program, now worth tens of millions, is a treasure trove of material on a ketamine nasal spray—including patents, clinical development plans, regulatory documents, and existing product inventories.

The new owner of the program, Washington-based biotech Marina, seems to understand what a goldmine they’ve landed on. The ketamine spray, which is halfway to completion, would be the first of its kind. Considering the estimated 30 million Americans who are currently on antidepressants, it could make a huge difference and garner millions of dollars in the process.

Marina CEO J. Michael French told reporters following the sale that he’s pushing full speed ahead to get something on the market. “We believe the early clinical successes of this program combined with broadening acceptance of ketamine as a treatment for neurological and psychiatric diseases, presents a unique opportunity to rapidly move this compound into the U.S. market as early as 2019,” he said.

Indeed research on ketamine, including the NIH study this week, has been promising. But the drug wasn’t always heralded as a breakthrough treatment.

Ketamine was synthesized in 1962 by a chemistry professor in Detroit, who was researching a less-hallucinogenic form of PCP. Two years later, the scientist began testing the drug on volunteers from a local prison. Belgium soon won a patent on the drug, and the Food and Drug Administration finally granted approval for its use in the U.S. in 1970.

The drug took off, with veterinarians using ketamine to anesthetize large animals and medics using it to treat soldiers in Vietnam. Short acting, it offered pain relief and sedation without depressing the respiratory system. The problem with ketamine was (and is) its high, which prompts a “trance-like state” that can turn dark and dangerous. It’s this that led to its recreational abuse, and monikers like Special K, Kit Kat, and Cat Valium.

In 2006, the National Institute of Health’s Dr. Carlos Zarate pioneered the first research on ketamine and depression. In his study, 18 individuals with severe, treatment-resistant depression were either given an IV of ketamine or a placebo, in two-day intervals. Those who received ketamine showed “significant improvement” leading Zarate to conclude that a single dose of ketamine could produce “robust and rapid antidepressant effects” within hours.

Studies in the years following yielded similar results, promoting ketamine clinics to open nationwide, offering intravenous doses of the drug for the severely depressed. The research was so promising that it led the Director of the National Institute of Mental Health Thomas Insel to post a letter in October 2014 expressing his support. “Recent data suggest that ketamine, given intravenously, might be the most important breakthrough in antidepressant treatment in decades,” he wrote.

There are three specific characteristics of ketamine that make it a potential breakthrough: it’s ability to take effect in a matter of hours, reduce suicidal thoughts, and target the most treatment-resistant forms of depression. The new study, published this week, attempted to solve one of the main problems.

One of the biggest appeals of ketamine is its ability to act quickly. Antidepressants on the market today can be effective, but often take as many as six weeks to fully kick in. For those so depressed they’re suicidal, that’s too long.

It’s a phenomenon that Scientific American writer Julianne Chiaet captured perfectly in an interview from 2013.“Kate wanted to die,” Chiaet writes. “She remembers the moment the psychiatrist said ‘the antidepressant isn’t going to work right away. Can you promise to be here next week and not kill yourself?’ ‘I told her no,’ Kate says.”

Ketamine infusions, in this case, could be lifesaving—and potentially already have been. On discussion forums housed by a group called the Ketamine Advocacy Network, certain users explain how the drug has helped them overcome incredibly dark times. One user who identifies as “Nigel H,” said the drug led him out of a “life of misery” where he was contemplating suicide.

“Nothing ever helped: meds, psychotherapy, meditation, exercise, diet, etc,” he writes. “Then I got ketamine and my world changed. At the time of my infusion, my acute symptoms included anhedonia, extreme anxiety, dysphoria, physical fatigue, and cognitive impairment, insomnia. Within a few hours after the infusion, the symptoms were 100 percent gone. I felt healthy, normal, happy.”

Not everyone has an experience as great as Nigel, it seems. While ketamine can have an effect on depression, it also carries with it a high that can be intolerable. Plus, without FDA approval, use of the drug is unregulated; meaning some shell out thousands for something they can’t even be sure is real. “Buyer beware,” a user named Ken writes, explaining that he paid more than $3,000 for six treatments. Others describe bad highs, some as “horrible” and “traumatic.”

The ketamine program that Shkreli’s company had been exploring was for an intranasal, rather than intravenous, delivery—one that studies have shown to be equally, if not more, effective.

But the problem of a potentially debilitating high remains. It’s this problem that the researchers at NIH were working to overcome—to pinpoint which part of ketamine has an antidepressant effect and remove it from the part that induces a high. What they found instead is that it’s not the ketamine itself but a metabolite that the body creates upon receiving it.

After zeroing in on this metabolite, researchers studied its effect in mice. The results were incredibly promising. The metabolite reversed the depression-like symptoms in mice without the dissociative, anesthetic, or addictive side effects. Published in Nature, the study suggests that ketamine treatment may not necessitate the high.

Zarate, who pioneered the ketamine-depression movement in 2006, called the study a breakthrough.

“This discovery fundamentally changes our understanding of how this rapid antidepressant mechanism works and holds promise for development of more robust and safer treatments,” he said. “By using a team approach, researchers were able to reverse-engineer ketamine’s workings from the clinic to the lab to pinpoint what makes it so unique.”

If the momentum surrounding ketamine as a treatment for depression continues, a nasal spray may soon be available in a drugstore near you. Thankfully, Shkreli won’t be the one selling it.